The present invention relates to polymer materials, and more particularly to thermal responsive, water-soluble polymers
Many polymer solutions exhibit a cloud point phenomenon, which occurs at the cloud point temperature, above or below which the polymer is soluble and the solution is clear, but below or above which it becomes insoluble and precipitates and solutions become opaque. In most polymer-solvent systems, solubility decreases with falling temperature, but in some cases involving polar polymers, the opposite occurs and the polymer suddenly precipitates at a specific, higher temperature, the cloud-point temperature, or lower critical solution temperature (LCST). If such clear to opaque transitions occur at a low enough temperature and are reversible, such polymer solutions or gels are useful in a variety of applications such as temperature dependent drug release systems or to isolate or purify specific compounds. Polymers which are thermally reversible and water soluble are among the so-called smart polymers.
It is a developing technique to apply water soluble smart polymers in chemical isolation and purification. The water soluble smart polymers are expected to be a key material in the fields of bio-medicine, environment, and resources. However, some problems encountered in conventional water soluble smart polymer application.
First, the reactive groups of conventional water soluble smart polymers are bonded only at two ends of the main chain polymers. The number of the reactive groups is insufficient for chemical purification,or isolation, which limits the scale of such processes. (Bioconjugate Chem., 4, 341-346 (1993))
Second, the gap between the LCST of thermal responsive, water soluble polymers and human body temperature goes beyond 3xc2x0 C., such as the polymers disclosed in U.S. Pat. No. 5,969,052 by Mumick, et al. The LCST of conventional thermal responsive, water soluble polymers are below 34xc2x0 C. and the operation range is narrow. Therefore, there is a difficulty to apply smart polymers to drug release in humans.
There is a need to provide a better thermal responsive, water soluble polymer to avoid the disadvantages above and to achieve wider application of smart polymers.
One object of the present invention is to provide a thermal responsive, water soluble polymer with a broad and adjustable range of cloud point.
Another object of the present invention is to provide a thermal responsive, water soluble polymer with a greater number of reactive functional groups to increase the chemical purification or isolation efficiency.
Still another object of the present invention is to provide a thermal responsive, water soluble polymer with a cloud point close to human body temperature (about 37xc2x0 C.) for temperature dependent drug release system application.
To achieve the above-mentioned objects, a thermal responsive, water soluble polymer according to the present invention comprises the co-polymerization product of: (a) 5xcx9c95 wt % of N-isopropyl acrylamide (NIP); (b) 0.1xcx9c80 wt % of 1-vinyl-2-pyrrolidinone (VPD); and optionally, (c) 0.1xcx9c30 wt % of acrylic acid (AA). The precipitation temperature of the polymer is adjustable by varying the proportion of the monomers above. As the proportion of component (b) VPD increases, the Lower Critical Solution Temperature (LCST) and the water solubility of the polymer increase. On the other hand, as the proportion of component (c) AA increases, the Lower Critical Solution Temperature (LCST) decreases and the COOH reactive groups increases, which impart high reactivity to the copolymer. By adjusting the proportion of the monomers, a broad range of the LCST can be manipulated and a larger number of reactive groups on the polymer is achieved.